Support is requested for a Keystone Symposia meeting entitled Long Noncoding RNAs: Marching toward Mechanism, organized by Thomas Cech, Edith Heard and Ronald R. Breaker. The meeting will be held in Santa Fe, New Mexico from February 27 - March 4, 2014. Much of the mammalian genome is transcribed into long non-coding RNAs, but their biological roles - such as transcriptional regulation via recruitment of histone- modifying enzymes - are only beginning to be discovered. At the same time, bacterial non-coding RNAs are being found to function as small-molecule-sensing riboswitches and as elements of the CRISPR defense system. For all of these biological systems, a key remaining problem is to understand the detailed mechanism of action. Listing and comparing all of the long ncRNAs, riboswitches, and CRISPR elements genome-wide and among species is useful, but how does the RNA function in each of these systems? The goal of this Keystone Symposia meeting is to stimulate conversations between scientists who work on these very diverse RNA systems, so they can share conceptual frameworks and experimental techniques. This goal will be accomplished by convening an exceptional group of academic and industrial scientists and students to share their insights.